Copy number variants tied to increased prostate cancer risk

(HealthDay News) -- Copy number variants (CNVs) of two loci are linked to a significantly higher risk of prostate cancer, according to a study published online April 10 in the Proceedings of the National Academy of Sciences.

Francesca Demichelis, Ph.D., from the Weill Cornell Medical College in New York City, and colleagues investigated CNVs associated with susceptibility to prostate cancer in 867 men with confirmed prostate cancer and 1,036 men without prostate cancer, all of Caucasian origin. The results were validated in an independent cohort of 346 men with prostate cancer and 454 men without prostate cancer, also of Caucasian origin.

The researchers identified two CNVs strongly associated with prostate cancer risk. One mapped to 15q21.3 (odds ratio, 2.78) and overlapped a noncoding enhancer element; further experiments suggested that the variant may interact with distant genes. The other variant mapped to the α-1,3-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase C (MGAT4C) gene on 12q21.31 (odds ratio, 4.8); further experiments showed that MGAT4C modulated the proliferation and migration of benign and cancer prostate cells. In metastatic versus localized cancer, MGAT4C was overexpressed. In the second cohort, these risk associations were replicated (15q21.3, combined P = 0.006; 12q21.31, combined P = 0.026).

"These findings establish noncoding and coding germ-line CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression," Demichelis and colleagues conclude.

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